The drug-drug interaction of phenytoin-folic acid is a clinical problem where one drug affects the other: 1) phenytoin decreases serum, red blood cell, and cerebral spinal fluid folate levels; and 2) supplementation of folic acid changes the concentration of phenytoin. The purpose of this study is to examine the impact of specific therapeutic regimens of 1 and 5 mg of oral folic acid on the disposition of phenytoin (Dilantin) in 16 healthy male volunteers who will have the pharmacokinetics of the anticonvulsant individually defined. The study will be divided into two phases: phase I will determine the pharmacokinetics of phenotyoin in each subject by defining their Vmax's (mg/day) and Km's (ug/ml); after a one week, drug free (washout) period between phases I and II, phase II will be divided into 4 treatment groups, that will study the effects of 1 and 5 mg of oral folic acid on phenytoin concentrations greater and less than the subject's Km(ug/ml). Since phase II consists of 4 treatment groups, a randomized block design will be used where each volunteer will serve as his own control in order to rule out enzyme induction by phenytoin. A drug-free (washout) period of 7 days will occur after the treatment group with a phenytoin concentration less than the subject's Km, and also a drug-free period of 7 days will occur after the treatment group with a phenytoin concentration greater than the subject's Km. Blood and urines will be collected on specified study days. Bloods will be centrifuged into serum, and ultracentrifugation will be used to separate free from bound fractions of phenytoin. A homogeneous enzyme immunoassay will be used to measure the concentrations of free and total phenytoin. A gas chromatographic/mass spectrometric method will be used to measure phenytoin, p-HPPH, methylated catechol, and dihydrodiol. Serum folates will be measured in the healthy volunteers throughout the study. Since two different concentrations of phenytoin will be used, the Vmax and Km will be determined after each dose of folic acid. The information gained from this study may provide the physician with a rational guide to the adjustment of the dose of phenytoin therapy when folic acid is added. However, if the dosing adjustments do not return the epileptic patient to the previous steady-state phenytoin concentration, then the low folate level may have an effect on the pharmacokinetics of phenytoin.